Uppsala University

About: Uppsala University is a education organization based out in Uppsala, Sweden. It is known for research contribution in the topics: Population & Gene. The organization has 36485 authors who have published 107509 publications receiving 4220668 citations. The organization is also known as: Uppsala universitet & uu.se.

Clinical pharmacokinetics of atorvastatin.

Abstract: Hypercholesterolaemia is a risk factor for the development of atherosclerotic disease. Atorvastatin lowers plasma low-density lipoprotein (LDL) cholesterol levels by inhibition of HMG-CoA reductase. The mean dose-response relationship has been shown to be log-linear for atorvastatin, but plasma concentrations of atorvastatin acid and its metabolites do not correlate with LDL-cholesterol reduction at a given dose. The clinical dosage range for atorvastatin is 10–80 mg/day, and it is given in the acid form. Atorvastatin acid is highly soluble and permeable, and the drug is completely absorbed after oral administration. However, atorvastatin acid is subject to extensive first-pass metabolism in the gut wall as well as in the liver, as oral bioavailability is 14%. The volume of distribution of atorvastatin acid is 381L, and plasma protein binding exceeds 98%. Atorvastatin acid is extensively metabolised in both the gut and liver by oxidation, lactonisation and glucuronidation, and the metabolites are eliminated by biliary secretion and direct secretion from blood to the intestine. In vitro, atorvastatin acid is a substrate for P-glycoprotein, organic anion-transporting polypeptide (OATP) C and H+-monocarboxylic acid cotransporter. The total plasma clearance of atorvastatin acid is 625 mL/min and the half-life is about 7 hours. The renal route is of minor importance (<1%) for the elimination of atorvastatin acid. In vivo, cytochrome P450 (CYP) 3A4 is responsible for the formation of two active metabolites from the acid and the lactone forms of atorvastatin. Atorvastatin acid and its metabolites undergo glucuronidation mediated by uridinediphosphoglucuronyltransferases 1A1 and 1A3. Atorvastatin can be given either in the morning or in the evening. Food decreases the absorption rate of atorvastatin acid after oral administration, as indicated by decreased peak concentration and increased time to peak concentration. Women appear to have a slightly lower plasma exposure to atorvastatin for a given dose. Atorvastatin is subject to metabolism by CYP3A4 and cellular membrane transport by OATP C and P-glycoprotein, and drug-drug interactions with potent inhibitors of these systems, such as itraconazole, nelfinavir, ritonavir, cyclosporin, fibrates, erythromycin and grapefruit juice, have been demonstrated. An interaction with gemfibrozil seems to be mediated by inhibition of glucuronidation. A few case studies have reported rhabdomyolysis when the pharmacokinetics of atorvastatin have been affected by interacting drugs. Atorvastatin increases the bioavailability of digoxin, most probably by inhibition of P-glycoprotein, but does not affect the pharmacokinetics of ritonavir, nelfinavir or terfenadine.

Pollination in Dianthus deltoides (Caryophyllaceae): effects of habitat fragmentation on visitation and seed set

Abstract: I analyse the effects of habitat fragmentation on the pollination success of a perennial, butterfly-pollinated, caryophyllaceous herb, the maiden pink, Dianthus deltoides L. The study was conducted in July 1986 and July 1987 at two different sites in southwest Sweden, an undisturbed “mainland” site and a fragmented site consisting of “habitat islands” within a heavily utilized agricultural area The fragmented area had a lower diversity and abundance of both flowering plants and flower-visiting insects. Dianthus flowers received fewer visits in the fragmented area than in the mainland area, and the seed set was much lower. Hand pollination increased seed set up to 4.1 times in the fragmented area, but no significant differences were found between hand-pollinated and control flowers at the mainland site. There were no differences between the two sites in standing crop of nectar, ovule number per flowers, or seed set of bagged flowers, band-pollinated flowers, and hand-pollinated fertilized flowers Thus, the difference in natural seed set between the two sites can be explained by differences in pollinator service. Resumen: Analize los efectos de fragmentacion de habitat sobre el exito de polinizacion de la hierba perenne, “caryophyllacedes, Dianthus deltoides L.” que es polinada por mariposas. Este estudio fue conducido en julio de 1986 y 1987 en dos diferentes lugares en el suroeste de Suecia, en un lugar pristino del continente y en un lugar fragmentado compuesto de “islas de habitat” dentro una area agricola summente utilizada. La area fragmentada tuvo una diversidad mas baja y una menor abunduncia de plantas florecentes y de insectos tipo visitantes de flores Las flores “Dianthus” recibieron menos visitas en las areas de habitat fragmentada que en la area del continente aun no modificado. La siembra tambien era mas baja. Polinizacion por mano aumento la siembra 4.1 veces mas en la area fragmentada, pero niguna diferencia significante fue encontrada entre las flores polinadas por mano y en el control en el lugar del continente. No bubo diferencias en cosechas paradas del nectar, numero de ovule por flor, o la siembra de flores de bolsas, flores polinadas por mano, y las flores fertilizadas y polinadas por mano, entre los dos lugares. Asi, la diferencia entre la siembra natural de los dos lugares puede ser explicado por las diferencias en el servicio de polinizacion.

Restorative experience and self-regulation in favorite places

Abstract: The authors report further evidence bearing on the relations among restorative experiences, self-regulation, and place attachment. University students (n = 101) described their favorite places and experiences in them, and 98 other students described unpleasant places. Natural settings were overrepresented among favorite places and underrepresented among the unpleasant places. In open-ended accounts, frequent mention of being relaxed, being away from everyday life, forgetting worries, and reflecting on personal matters indicated a link between favorite places and restorative experience. Restoration was particularly typical of natural favorite places. Structured evaluations of being away, fascination, coherence, and compatibility indicated they were experienced to a high degree in the favorite places, although fascination to a lesser degree than compatibility. The favorite and unpleasant places differed substantially in all four restorative qualities but especially in being away and compatibility. Self-refe...

Business Networks and Cooperation in International Business Relationships

Abstract: Cooperative relationships between firms can be better understood if they are examined in the context of a network of connected business relationships. Based on research on business relationships and business networks, this paper formulates a LISREL model that analyses cooperation in international business relationships between suppliers and customer firms. Theory suggests that cooperation can raise the value of business relationships, and that business network connections have an impact on cooperation. The model is investigated in a sample of 136 international business relationships. The analysis shows that relationship profitability is directly affected by relationship commitment and, indirectly through commitment, by business network connections.